Optimization of the TB Treatment Regimen Cascade (OneRIF)

Damien Foundation

Status and phase: Completed; Phase 3

Conditions: Tuberculosis, Pulmonary

Treatments: Drug: double rimfampicin; Drug: Standard TB treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT02153528

OneRIF

Details and patient eligibility

About

• Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. 2 retreatment regimen

• General study design: This open label, randomised clinical trial is intended as a pilot study on the efficacy and safety of high-dose rifampicin and feasibility and added value of auramine and/or FDA vital staining sputum smear after 2 weeks of intensive treatment phase. If this proof-of-concept study provides substantial indication of benefit without indication of excess toxicity, the data from the study will be used to design a larger scale, cluster-randomized study. The aim of this cluster randomised study would be to provide definite proof of the benefit of the intervention on adverse treatment outcomes and lack of excess toxicity associated with high dose rifampicin. In addition, the cluster-randomized study would provide a more precise assessment of the suppression and prevention of (acquired) resistance endpoints.

An interim analysis is thus planned at the time the last recruited patient finishes treatment, i.e. about 9 months after the end of recruitment. It will focus on assessment of drug toxicity versus suggested benefits of the intervention. This analysis will be primarily performed for the go/no-go decision and design considerations for the cluster-randomized trial. The decision on proceeding to the cluster randomized study will be based on the absence of excess toxicity, a trend toward a reduction of unfavourable outcomes (excluding relapse), and possible favourable effects on initially present low-resistance mutations / mutations acquired during treatment. It will also allow to adapt the design of the larger study particularly regarding the algorithm for resistance screening, and whether or not treatment shortening could be justified with rapid initial conversion.

Enrollment: 701 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosed with smear-positive pulmonary TB
• 15 years or older
• Able and willing to provide written informed consent

Exclusion criteria

• contacts of MDR-TB patients and other MDR-TB suspects diagnosed with resistance on rapid DST for rifampicin performed prior to start of treatment according to NTP guidelines
• smear-negative pulmonary and extra-pulmonary TB cases
• patients in need of hospitalization because of very bad general condition or complications
• patients with clinically active liver disease, for the study defined as jaundice confirmed by a local Medical Officer (Government)
• any known HIV-positive patient (although none are expected)
• any patient with known hepatitis B or C infection
• pregnant women; in addition, patients in the intervention arm who become pregnant during treatment will be switched to the control arm

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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701 participants in 2 patient groups

Standard TB treatment

Active Comparator group

Description:

Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease

Treatment:

Drug: Standard TB treatment

double rimfampicin

Experimental group

Description:

2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout

Treatment:

Drug: double rimfampicin